The overall objective of this project is to investigate the mechanism of failure of central nervous system (CNS) regeneration in mammals. An understanding of this mechanism will facilitate the search for neuroregenerative agents. Th retina is used as a model system for technical reasons. The advantage of the retina lies in the fact that it can be flat-mounted. This facilitates the examination of silver-stained axons in that their course of growth, directionality, degree of fasciculation and elongation can be assessed while avoiding the tedium and errors of serial section reconstruction. The project in its present phase involves comparative studies of the reaction of optic axons in the ganglion cell fiber layer of lesioned retinas at various developmental ages and in various species. These studies will compare the morphological responses to such lesions in regenerating and non-regenerating systems. The techniques consist of specific stains for optic fibers, glia and connective tissue at the light microscopic level and histochemical stains for intercellular matrix at the electron microscopic level. In other expeiments we will assess whether adult mammalian optic fibers, having bypassed a small retinal lesion, will continue to grow normally, and whether fibers will grow retrograde back into the retina, following optic nerve crush.